Obesity is usually defined as a body weight more than 20% in excess of the ideal body weight. Obesity is associated with an increased risk for cardiovascular disease, diabetes and an increased mortality rate (see Grundy et al., Disease-a-Month 36:645-696, 1990). Treatment for obesity includes diet, exercise and surgery (Leibel, R. L. et al., New England Journal of Medicine 332:621-628, 1995).
At least five single-gene mutations resulting in obesity have been described in mice, implicating genetic factors in the etiology of obesity (Friedman et al., Cell 69:217-220, 1990). In the ob mouse, a single gene mutation, obese, results in profound obesity, which is accompanied by diabetes (Friedman et al., Genomics 11:1054-1062, 1991). Cross-circulation experiments have suggested that ob mice are deficient of a blood-borne factor regulating nutrient intake and energy metabolism (Coleman, D. L., Diabetologia 14:141-148, 1978).
Zhang et al., Nature 372:425-432, 1994, not admitted to be prior art, describe cloning and sequencing the mouse ob gene and its human homologue. They indicate that the ob gene is exclusively expressed in white adipose tissue.